Acute Porphyrias

Related Subjects: | Acute Porphyrias | Variegate Porphyria | Acute Intermittent Porphyria (AIP) | Porphyria Cutanea Tarda (PCT) | Porphyria Testing

Acute porphyrias are hereditary disorders of haem biosynthesis; they have a prevalence of about 1 in 75 000 of the population. BNF states that if no safe alternative, drug treatment for serious or life-threatening conditions should not be withheld from patients with acute porphyria.

About

• Disruption of Heme synthetic pathway
• Build up of precursors causes toxicity
• Great care must be taken when Prescribing

National UK Links

• See BNF Here for more advice
• See the Safe Drug List 2018
• National Acute Porphyria Service

Causes

• Acute Intermittent Porphyria
• Variegate Porphyria
• Hereditary Coproporphyria
• Delate ALA dehydrase deficiency

Precipitant

• Hormonal changes in women and menstrual cycle
• Drugs : check all in BNF or equivalent
• Low calories. Low carbohydrate diets. Fasting. Nil by mouth (NPO)
• Alcohol, Organic solvents, Infections,Surgery, Stress

Drugs to avoid - See BNF for more

• Anabolic steroids
• Antidepressants, MAOIs (contact UKPMIS for advice)
• Antidepressants, Tricyclic and related (contact UKPMIS for advice)
• Barbiturates (includes primidone and thiopental)
• Contraceptives, hormonal (contact UKPMIS or a porphyria specialist)
• Hormone replacement therapy (for detailed advice contact UKPMIS or a porphyria specialist)
• Imidazole antifungals (PO/IV use; topical antifungals safe due to low systemic exposure)
• Non-nucleoside reverse transcriptase inhibitors (contact UKPMIS for advice)
• Progestogens (for detailed advice contact UKPMIS or a porphyria specialist)
• Protease inhibitors (contact UKPMIS for advice)
• Sulfonamides (includes co-trimoxazole and sulfasalazine)
• Sulfonylureas (glipizide and glimepiride are thought to be safe)
• Taxanes (contact UKPMIS for advice)
• Triazole antifungals (applies to oral and intravenous use; topical antifungals are thought to be safe due to low systemic exposure)

Clinical

• Abdominal Pain and Neurological symptoms
• Muscle weakness which can involve respiratory muscles
• Delirium, progressive paralysis, Tetraplegia
• Psychosis, hallucinations, Constipation, fatigue, irritable
• Can last hours days even weeks
• Tachycardia is often an indicator of disease state progression.
• VP/HCP can have bullous eruptions on sun exposed areas
• Abdominal exam does not match the pain severity.
• Urine can be Red brown urine.

Investigations

• Bloods may be normal or WCC minimally elevated
• Urine screen for PBG and if positive then quantitative ALP and PBG levels which are x 5 normal
• AIP: measure PBG deaminase and Genetic analysis

BNF: Haem arginate is administered by short intravenous infusion as haem replacement in moderate, severe, or unremitting acute porphyria crises. In the United Kingdom the National Acute Porphyria Service (NAPS) provides clinical support and treatment with haem arginate from two centres (Cardiff and Vale University Health Board and King's College Hospital) (see Useful resources).

Drugs to avoid (check all): Diclofenac, Alcohol, OCP, HRT, TCA, Benzodiazepines, Anaesthetic agents (barbiturates, halothane), Antibiotics (cephalosporins, sulfonamides, macrolides, tetracyclines, rifampicin, trimethoprim, chloramphenicol, metronidazole), Metoclopramide, ACEI, CCB, Statins, Anticonvulsants, Furosemide, Sulfonylureas, Lidocaine, Gold salts, Antihistamines, Amphetamine

Management

• In the UK contact National Acute Porphyria Service (NAPS) linked above
• ABC, Close monitoring. Dark quiet room.
• Eliminate triggers. Consider Dextrose (IV or oral)
• Hematin or Heme Arginate which can cause VTE
• Oral or IV Dextrose: 3 L of 10% dextrose over 24 hrs
• Hypertension and tachycardia may be treated with Beta blockers

Prevention

• Avoid heavy alcohol, starvation, causative drugs
• VP/HCP avoid sun exposure or wear sun blocks
• ↑ Risk of hepatocellular carcinoma so needs surveillance

References

• Best practice guidelines on clinical management of acute attacks of porphyria and their complications
• Here for more advice at British National Formulary
• More information can be found here at European Porphyria Network